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ORIGINAL RESEARCH article
Front. Immunol.
Sec. Vaccines and Molecular Therapeutics
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1566225
This article is part of the Research TopicNext-Generation Vaccines Against Arboviruses: Innovations in Design, Delivery, and Immunological InsightsView all 3 articles
The MVA-VP2-NS1-2A-NS2-Nt vaccine candidate provides heterologous protection in sheep against Bluetongue virus
Provisionally accepted
Luis Jiménez-Cabello
Sergio Utrilla-TrigoMiguel Illescas-AmoKaren Rodríguez-Sabando
Julio Benavides
Javier Ortego
EVA CALVO-PINILLA*- Spanish National Research Council (CSIC), Madrid, Spain
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Bluetongue (BT) is an important arthropod-borne livestock disease transmitted by Culicoides midges. The etiological agent, Bluetongue virus (BTV), can lead to severe economic losses due to reduced productivity and trade restrictions. Nowadays, classical vaccines based on inactivated viruses are used to control outbreaks but do not confer multiserotype protection, which reinforces the idea of pursuing research into developing strategies that enhance the immune response directed to conserved antigenic regions, aiming broader protection across multiple serotypes. Recently, we described a vaccine candidate that confers full protection against a homologous serotype of BTV based on recombinant Modified Vaccinia Virus Ankara (MVA) co-expressing the highly conserved BTV nonstructural protein NS1 and the N-terminal end of NS2 along with protein VP2 of BTV-4. In this work, we evaluated the multiserotype protective capacity of this recombinant vaccine candidate in sheep after infection with the heterologous virus BTV-8, achieving a significant blockade of viral replication and attenuation of the clinical singns induced by BTV. After infection, vaccinated animals showed more regulated pro-inflammatory cytokine levels compared to non-vaccinated sheep. In addition, we noticed the induction of potent T cell immune responses specific to NS1 and NS2-Nt proteins of BTV, mainly based on CD8+ T cells, which could mediate the protection against BTV-8. Moreover, stimulated immunized sheep PBMCs with BTV antigens triggered the secretion of IL-6, IL-1β, IL-1α, IL-17a, IL-10 and IFNγ, cytokines that play crucial roles in initiating immune responses. Con formato: Español (España) Con formato: Español (España) Con formato: Español (España) Con formato: Español (España)
Keywords: Bluetongue virus (BTV), Orbivirus, Vaccine, MVA, DIVA, Multiserotype, Sheep
Received: 24 Jan 2025; Accepted: 15 Apr 2025.
Copyright: © 2025 Jiménez-Cabello, Utrilla-Trigo, Illescas-Amo, Rodríguez-Sabando, Benavides, Ortego and CALVO-PINILLA. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: EVA CALVO-PINILLA, Spanish National Research Council (CSIC), Madrid, Spain
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